Anthracyclines form one of the largest families of naturally occurring bioactive compounds. Several members of this family have shown to be clinically effective anti-neoplastic agents. These include, for example, daunorubicin, doxorubicin, idarubicin, epirubicin, pirarubicin, zorubicin, aclarubicin, and carminomycin. For instance, these compounds have shown to be useful in treatment of breast carcinoma, acute lymphocytic and non-lymphocytic leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and other solid cancerous tumors.
Anthracyclin antibiotics possess very high antineoplastic activity allowing for their effective application in the treatment of a wide spectrum of tumors. The starting material for the synthesis of the majority of anthracyclin antibiotics is Daunorubicin having the form shown in Formula (2). Epirubicin of Formula (1) differs from Daunorubicin which is produced by fermentation, by having a 14-oxymethyl group and equatorial orientation of the HO-4′-C.

Conversion of Daunorubicin to Epirubicin is achieved by the oxidation of 4′-hydroxyl fragment to ketone, accompanied by a loss of the optical center, with additional stereospecific reduction (in a needed conformation) and further transformation of the epi-daunorubicin to epirubicin via bromination of the 14-CH3—(CO)-fragment and hydrolysis of the resulting 14-CH2Br-fragment to-(CO)—CH2OH radical. This process is shown diagrammatically in Diagram 1, below.

This synthetic pathway was developed by Farmitalia as described in U.S. Pat. No. 4,345,068 to Suarato et al. Other methods of epi-daunorubicin synthesis have been previously described, for example, in U.S. Pat. No. 5,945,518 to Bigatti et al. and U.S. Pat. No. 5,874,550 to van der Rijst et al. However, all existing methods of synthesizing epi-daunorubicin utilize the same starting material, namely Daunorubicin of Formula (2).